Currently, traumatic brain injury (TBI) is the leading cause of death or of disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) make the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival, and long term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with
poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p<0.001) and in both ipsi- (p<0.001) and contralateral (p<0.001) parts of brain in TBI mice compared to controls. The present study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 hours post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the
injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively deliver BDNF into the brain, and improve neurological and cognitive deficits in TBI mice, thereby providing a neuroprotecti